Genetic variation of the serotonin 2a receptor affects hippocampal novelty processing in humans

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in sev...

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Bibliographic Details
Published in:PloS one 2011-01, Vol.6 (1), p.e15984-e15984
Main Authors: Schott, Björn H, Seidenbecher, Constanze I, Richter, Sylvia, Wüstenberg, Torsten, Debska-Vielhaber, Grazyna, Schubert, Heike, Heinze, Hans-Jochen, Richardson-Klavehn, Alan, Düzel, Emrah
Format: Article
Language:English
Subjects:
Adult
Alarm systems
Behavior disorders
Biology
Cognitive ability
Experiments
Familiarity
Functional magnetic resonance imaging
Gene polymorphism
Genetic aspects
Genetic diversity
Genetic polymorphisms
Genotype
Hippocampus
Hippocampus - physiology
Homozygotes
Humans
Intracellular signalling
Learning
Learning - physiology
Magnetic resonance
Magnetic Resonance Imaging
Medicine
Memory
Memory - physiology
Mutation, Missense
Neurobiology
Neurology
Neuromodulation
Neurosciences
NMR
Novelty
Nuclear magnetic resonance
Phenols (Class of compounds)
Polymorphism
Polymorphism, Genetic
Psychotropic drugs
Receptor, Serotonin, 5-HT2A - genetics
Recognition
Recognition (Psychology) - physiology
Serotonin
Social and Behavioral Sciences
Stimuli
Young Adult
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Summary:Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0015984